Calcium carbonate does not affect imatinib pharmacokinetics in healthy volunteers

Hussein Tawbi, Susan M. Christner, Yan Lin, Matthew Johnson, Emily T. Mowrey, Craig Cherrin, Edward Chu, James J. Lee, Shannon Puhalla, Ronald Stoller, Leonard R. Appleman, Brian M. Miller, Jan H. Beumer

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Purpose: Imatinib mesylate (Gleevec®/Glivec®) has revolutionized the treatment of chronic myeloid leukemias and gastrointestinal stromal tumors, and there is evidence for an exposure response relationship. Calcium carbonate is increasingly used as a calcium supplement and in the setting of gastric upset associated with imatinib therapy. Calcium carbonate could conceivably elevate gastric pH and complex imatinib, thereby influencing imatinib absorption and exposure. We aimed to evaluate whether use of calcium carbonate has a significant effect on imatinib pharmacokinetics. Methods: Eleven healthy subjects were enrolled in a 2-period, open-label, single-institution, randomized crossover, fixed-schedule study. In one period, each subject received 400 mg of imatinib p.o. In the other period, 4,000 mg calcium carbonate (Tums Ultra®) was administered p.o. 15 min before 400 mg of imatinib. Plasma concentrations of imatinib and its active N-desmethyl metabolite CGP74588 were assayed by LC-MS; data were analyzed non-compartmentally and compared after log transformation. Results: Calcium carbonate administration did not significantly affect the imatinib area under the plasma concentration versus time curve (AUC) (41.2 μg/mL h alone vs. 40.8 μg/mL h with calcium carbonate, P = 0.99), maximum plasma concentration (C max) (2.35 μg/mL alone vs. 2.39 μg/mL with calcium carbonate, P = 0.89). Conclusions: Our results indicate that the use of calcium carbonate does not significantly affect imatinib pharmacokinetics.

Original languageEnglish (US)
Pages (from-to)207-211
Number of pages5
JournalCancer Chemotherapy and Pharmacology
Volume73
Issue number1
DOIs
StatePublished - Jan 2014
Externally publishedYes

Keywords

  • Calcium
  • CML
  • GIST
  • Imatinib
  • Interaction

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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